Inhibition of H9N2 Virus Invasion into Dendritic Cells by the S-Layer Protein from L. acidophilus ATCC 4356

Abstract

Probiotics are essential for the prevention of virus invasion and the maintenance of the immune balance. However, the mechanism of competition between probiotics and virus are unknown. The objectives of this study were to isolate the surface layer (S-layer) protein from L. acidophilus ATCC 4356 as a new antiviral material, to evaluate the stimulatory effects of the S-layer protein on mouse dendritic cells (DCs) and to verify its ability to inhibit the invasion of H9N2 avian influenza virus (AIV) in DCs. We found that the S-layer protein induced DCs activation and up-regulated the IL-10 secretion. The invasion and replication of the H9N2 virus in mouse DCs was successfully demonstrated. However, the invasion of H9N2 virus into DCs could be inhibited by treatment with the S-layer protein prior to infection, which was verified by the reduced hemagglutinin (HA) and neuraminidase (NA) mRNA expression, and nucleoprotein (NP) protein expression in the DCs. Furthermore, treatment with the S-layer protein increases the Mx1, Isg15, and Ddx58 mRNA expressions, and remits the inflammatory process to inhibit H9N2 AIV infection. In conclusion, the S-layer protein stimulates the activation of mouse DCs, inhibits H9N2 virus invasion of DCs, and stimulates the IFN-I signaling pathway. Thus, the S-layer protein from Lactobacillus is a promising biological antiviral material for AIV prevention.

Surface (S) Layer Proteins of Lactobacillus acidophilus Block Virus Infection via DC-SIGN Interaction

“…The S-layer protein was immobilized on the ELISA plate, incubated with the respective DC-SIGN-hFc fusion proteins, and their interaction was quantitated by colorimetric detection (Figure 3A). As expected, a direct interaction was observed by this binding assay (Konstantinov et al, 2008; Lightfoot et al, 2015; Gao et al, 2016). We determined the calcium dependence of the DC-SIGN/S-layer interaction, incubating the proteins in the presence of EGTA.…”

“…They are considered to function as protective coats, in the maintenance of cell shape, in ion exchange in the cell wall, and in adhesion to biotic and abiotic surfaces. We and others have shown that the interaction between the S-layer of Lactobacillus acidophilus , one of the major bacterial species found in human intestines, and DC-SIGN can act as a potent inhibitor of JUNV and H9N2 viral infections (Martínez et al, 2012; Gao et al, 2016; Prado Acosta et al, 2016). Given that L. acidophilus and S-layer are both categorized as “generally recognized as safe” (GRAS) (Dunne et al, 2001; Mohamadzadeh et al, 2008), there is interest in further characterizing this novel mechanism of inhibition in order to develop new therapeutics that would target alphaviruses and flaviviruses.…”

Role of Probiotics in Stimulating the Immune System in Viral Respiratory Tract Infections: A Narrative Review

“…Similarly, mouse adapted influenza A virus (PR8) titer was reduced in RAW264.1 cells by L. gasseri SBT2055 [ 60 ]. In mouse bone marrow DCs, the inhibition of viral replication by L. acidophilus ATCC4356 S-layer protein was demonstrated [ 62 , 63 ]. Priming of cells with S-layer protein prior to H9N2 avian influenza virus infection inhibited the invasion and replication of the virus, stimulated the type I IFN signaling pathway, increased IL-10 mRNA, and decreased TNF-α mRNA expression [ 62 ].…”

Extractable Bacterial Surface Proteins in Probiotic–Host Interaction

“…DC-SIGN is a CLR present in DCs and macrophages, it is involved in the recognition of several viruses and other microbes, a key step in the entry of pathogens into the cell. Indeed, L. acidophilus ATCC4356 Slps stimulate the activation of mouse DCs by activating IFN-I signaling pathway, which inhibit invasion of DCs by influenza virus H9N2 ( Gao et al, 2016 ). In addition, L. acidophilus ATCC4356 Slps inhibit the Junin virus (JUNV) infection by interacting with DC-SIGN ( Martínez et al, 2012 ).…”